Vitamin E supplements probably aren't doing anything to prevent the development of heart failure in women, an analysis of the Women's Health Study showed.

After adjustment for potential confounders, taking 600 IU of vitamin E every other day was not associated with incident heart failure (HR 0.93, 95% CI 0.71 to 1.21, P=0.59), according to Claudia Chae, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues.

But because there were relatively few heart failure events during follow-up, a small-to-moderate effect of supplementation could not be excluded, the researchers reported online in Circulation: Heart Failure.

"These results underscore the importance of focusing on other primary prevention measures proven to reduce the risk of future heart failure, including effective control of blood pressure and the primary prevention of coronary artery disease," they wrote, echoing statements from the American Heart Association on the subject.

"Scientific evidence does not suggest that consuming antioxidant vitamins can eliminate the need to reduce blood pressure, lower blood cholesterol, or stop smoking cigarettes," according to the association's website.

In fact, although oxidative stress may be involved in the development of heart failure, antioxidant therapy has been associated with a greater risk of incident heart failure and hospitalization for heart failure among patients with vascular disease or diabetes in the HOPE trial and a nonsignificant elevation in heart failure risk among patients with a recent MI in the GISSI-Prevenzione trial.

But no large trials have evaluated the use of antioxidant therapy for the primary prevention of heart failure.

To explore the issue, Chae and colleagues turned to the Women's Health Study, a randomized, placebo-controlled trial of low-dose aspirin, vitamin E, and beta carotene for the primary prevention of cardiovascular disease and cancer. The current analysis included 39,815 initially healthy women ages 45 and older at baseline (mean age 54.6).

Over a median follow-up of 10.2 years, 220 women developed heart failure -- 106 randomized to vitamin E and 114 randomized to placebo.

After adjustment for age and randomized aspirin and beta carotene treatment, supplementation with vitamin E was not associated with heart failure risk. The association remained after further adjustment for other risk factors, including interim MI, and limiting the analysis to definite heart failure cases only.

In a prespecified subgroup analysis, there was some evidence of a benefit for heart failure with preserved ejection fraction (diastolic heart failure).

"This finding should be interpreted with caution, since it was a subgroup analysis based on a relatively small number of heart failure cases, but it nevertheless merits further study," the authors wrote.

If the finding "is confirmed in other prospective studies, then future randomized trials of antioxidant therapy in patient populations at high risk for diastolic heart failure may be warranted."

Chae and colleagues speculated that differences among the patient populations might explain why there was a suggestion of harm from vitamin E supplementation in the HOPE and GISSI-Prevenzione trials. In particular, the current trial was a primary prevention study, whereas the other two were secondary prevention studies.

In addition, the secondary prevention trials had relatively small populations of women and higher rates of heart failure. Doses and dosing regimens of vitamin E also differed between the trials.

The authors acknowledged that the findings of the current study may not apply to populations beyond the healthy, middle-age, mostly white females who participated.

Other limitations included the inability to assess the differential effects of vitamin E in women with or without valvular heart disease, possible variation in the measurements of ejection fraction, which were taken from medical records, and the self-report of heart failure events.

The study was supported by the Elizabeth Anne and Karen Barlow Corrigan Women's Heart Health Program at Massachusetts General Hospital, the Donald W. Reynolds Foundation, and grants from the National Heart, Lung and Blood Institute and the National Cancer Institute.

The authors reported that they had no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.